GENETIC AND MOLECULAR ANALYSIS OF OLFACTION

Yale University, New Haven CT

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Abstract

DESCRIPTION: This proposal aims to elucidate basic principles underlying olfactory system function, organization, and development. Mechanisms of signal transduction, patterns of neuronal organization, and fundamental rules governing olfactory system development may be incisively addressed in simple olfactory systems consisting of limited numbers of neurons, in organisms which can be investigated by a variety of forceful means. The Drosophila olfactory system is such a system, as it consists of approximately 103 neurons, and is amenable to convenient genetic, molecular, physiological, and behavioral analysis. An intriguing question in the field of olfaction is how olfactory neurons acquire their diverse identities. This proposal calls for detailed analysis of a gene, ajc6, whose mutations severely reduce physiological response to some, but not all, odors. acj6 has recently been found to be identical to the I-POU gene, which encodes a POU-domain transcription factor. Anatomical, physiological, genetic, and molecular experiments are proposed to determine the cellular basis of the mutant phenotype, and to determine whether I-POU plays a key role in the development of neuronal subsets in the olfactory system, as do certain POU genes in the mammalian visual and auditory systems. The possibility that I-POU acts in concert with other POU genes, perhaps combinatorially, will be investigated. The proposal also aims to elucidate basic principles of olfactory system organization by recording from individual neurons in situ. This study will also lay a foundation for analyzing the cellular physiology of selected mutants, including ajc6 and another odorant-specific mutant, and mutants with abnormalities affecting phospholipase C, a sodium channel, and a nitric oxide synthase (NOS). A genetic analysis of the anosmic mutant is proposed. This mutant is abnormal in olfactory response and in olfactory adaptation. Interestingly, it contains reduced levels of NOS in its olfactory system. Further analysis is designed to investigate the role of anosmic in olfactory system signalling and/or development.